SOCS3 methylation mediated the effect of sedentary time on type 2 diabetes mellitus: The Henan Rural Cohort study

Liu, Xiaotian; Qian, Xinling; Tu, Runqi; Mao, Zhenxing; Huo, Wenqian; Zhang, Haiqing; Jiang, Jingjing; Zhang, Xia; Tian, Zhongyan; Li, Yuqian; Wang, Chongjian

doi:10.1016/j.numecd.2019.11.007

Cited by 10 publications

(7 citation statements)

References 29 publications

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“…SOCS3 methylation was found to have a significantly negative association with prevalence of T2DM in this present study. Similar results were reported in previous studies [ 22 , 30 – 34 ]. For example, available evidence from a nested case–control study in Asians and Europeans suggested that SOCS3 methylation was associated with future T2DM, and the relative risk was 0.94 (0.92–0.96) [ 30 ].…”

Section: Discussionsupporting

confidence: 93%

Combined effects of progesterone and SOCS3 DNA methylation on T2DM: a case–control study

et al. 2021

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Background This study aims to investigate the independent and combined effects of progesterone and suppressor of cytokine signaling (SOCS)-3 DNA methylation on type 2 diabetes mellitus (T2DM) among men and postmenopausal women in rural China. Methods A case–control study with 914 participants (329 T2DM, 585 controls) was conducted. Serum progesterone was detected with liquid chromatography-tandem mass spectrometry. DNA methylation of SOCS3 was determined by MethylTarget™. Linear regression was applied to evaluate the associations of progesterone and SOCS3 methylation with marks of glucose metabolism. Logistic regression was employed to investigate the independent and combined effects of progesterone and SOCS3 methylation with T2DM in men and postmenopausal women. Results After multiple adjustment, progesterone was positively associated with T2DM in both men (odds ratio (OR) (95% confidence interval (CI)): 2.77 (1.79, 4.29)) and postmenopausal women (OR (95% CI): 1.85 (1.26, 2.72)). Methylation level of Chr17:76,356,190 or Chr17:76,356,199 (SOCS3) was negatively associated with T2DM in both men (OR (95% CI): 0.58 (0.39, 0.86) or 0.27 (0.14, 0.51)) and postmenopausal women (OR (95% CI): 0.43 (0.29, 0.65) or 0.53 (0.28, 0.99)). Subjects with high progesterone and low Chr17:76,356,190 or Chr17:76,356,199 methylation were more susceptible to have a higher prevalence of T2DM (men: OR (95% CI): 5.20 (2.49, 10.85) or 5.62 (2.74, 11.54); postmenopausal women: OR (95% CI): 3.66 (1.85, 7.26) or 3.27 (1.66, 6.45)). Conclusions The independent and combined effects of progesterone and SOCS3 methylation on T2DM were found among men and postmenopausal women, suggesting that ensuring low levels of progesterone and high methylation of SOCS3 could reduce the prevalence of T2DM. Trial registration The Chinese Clinical Trial registration: The Henan Rural Cohort Study, ChiCTR-OOC-15006699. Registered 06 July 2015, http://www.chictr.org.cn/showproj.aspx?proj=11375

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Section: Discussionsupporting

confidence: 93%

Combined effects of progesterone and SOCS3 DNA methylation on T2DM: a case–control study

et al. 2021

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“…The possible reason for the difference may due to racial differences in the study population. Our previous study has also explored the association between SOCS3 methylation and T2D, 6 however, it just included one DNA methylation site (Chr17:76356190), the current study extended the two DNA methylation sites (Chr17:76356190 and Chr17:76356199) and differentiated the effects between the gender.…”

Section: Discussionmentioning

confidence: 99%

“…Whole Blood Genomic DNA Extraction Kit III (Magnetic bead) (Bioteke Corporation, Beijing, China) was used to extract genomic DNA. Four CpG regions were selected and sequenced in the SOCS3 gene; the details have been described before 6 and summarized in supplement data. Four pair primer sequences were designed to detect the methylation level of four genomic regions of SOCS3 gene, which included 93 CpG sites (as shown in Table S1).…”

Section: Dna Extraction and Methylation Analysis Of Socs3mentioning

confidence: 99%

“…5 Additionally, our previous study found a negative correlation between Chr17:76356190 (SOCS3) methylation and T2D. 6 However, the Botnia prospective study in Finland found that cg18181703 (SOCS3) methylation had no effect on the prevalence of T2D. 7 Importantly, most of studies are focused on the western populations, and there is seldom evidence of an association of SOCS3 methylation with T2D in rural regions of China.…”

Section: Introductionmentioning

confidence: 98%

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The mediation role of SOCS3 methylation in the effect of serum testosterone on type 2 diabetes

Wang

Liu

Wei

et al. 2021

Journal of Diabetes

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Background: Previous studies reported that testosterone and DNA methylation of suppressor of cytokine signaling-3 (SOCS3) were associated with type 2 diabetes (T2D). Testosterone affects SOCS3 gene expression. Therefore, we aimed to investigate how the SOCS3 methylation mediates the relationship between testosterone and T2D among Chinese rural adults.Methods: A case-control study comprised 365 T2D patients and 651 controls was conducted. Liquid chromatography-tandem mass spectrometry and MethylTarget were used to determine the levels of serum testosterone and DNA methylation of SOCS3 gene, respectively. The odds ratio (OR) of testosterone or SOCS3 methylation for T2D was calculated using logistic regression models, and β value of testosterone for SOCS3 methylation was evaluated by linear regression models. Furthermore, through mediation analysis the mediating effect of SOCS3 methylation on the association of testosterone with T2D was estimated. Results: After adjusting for multiple variables, the protective effect of testosterone on T2D was found in men (OR = 0.61, 95% confidence interval [CI]: 0.47-0.80), and the methylation of Chr17:76356190 or Chr17:76356199 was negatively related to T2D in both men and women. Moreover, testosterone was positively associated with Chr17:76356190 methylation in men and Chr17:76356199 methylation in women (both P < .05). The mediation analysis

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“…The ARm status was evaluated using whole blood for each individual using Whole Blood Genomic DNA Extraction Kit III (Magnetic bead) (Bioteke Corporation, Beijing, China) according to the manufacturer's instructions. Specific DNA methylation was assessed through the target region MethylTarget (Genesky Corporation, Shanghai, China) following genomic DNA isolation and bisulfite sequencing 23,24 . We investigated specifically two CpG islands (Length 234 (66764189‐66 763 956) and Length 185 (66766038‐66 766 222)) located in the AR promoter, relative to the translational start site.…”

Section: Methodsmentioning

confidence: 99%

Androgen receptor DNA methylation is an independent determinant of glucose metabolic disorders in women; testosterone plays a moderating effect

Huo

Zhang³

et al. 2020

Journal of Diabetes

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Background We have previously shown that serum testosterone was associated with impaired fasting glucose (IFG) and type 2 diabetes (T2D). Testosterone can be acting through binding the androgen receptor (AR). Therefore, we aimed to explore the independent associations of AR DNA methylation (ARm) with IFG and T2D and the moderation effects of serum testosterone on the associations. Methods A case‐control study with 1065 participants including 461 men and 604 women was performed. ARm in peripheral blood sample and serum testosterone were measured using pyrosequeuncing and liquid chromatography‐tandem mass, respectively. Multivariable logistic regression was performed to estimate the associations of ARm (including 2 cytosine‐phosphoguanine [CpG] islands and average methylation levels) with different glucose status. Serum testosterone was used as a moderator to estimate the moderation effect. Results After multivariate adjustment, CpG 1, 2 and CpG average methylation were all significantly associated with IFG (CpG 1: Odds ratio (OR) = 4.80, 95% confidence interval (CI): 2.24‐10.27; CpG 2: OR = 4.35, 95% CI: 2.50‐7.58; CpG average: OR = 11.73, 95% CI: 5.36‐25.67) in women. In addition, testosterone played negative moderation effects in above associations. Moreover, no significant independent associations of methylation levels with T2D was observed both in men and women. Conclusion Our findings demonstrate that ARm was positively associated with IFG in women and the associations would be weakened by testosterone. The individuals experiencing low testosterone and ARm levels reported a lower state of IFG than those who experienced high levels of testosterone and ARm in women.

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SOCS3 methylation mediated the effect of sedentary time on type 2 diabetes mellitus: The Henan Rural Cohort study

Cited by 10 publications

References 29 publications

Combined effects of progesterone and SOCS3 DNA methylation on T2DM: a case–control study

Combined effects of progesterone and SOCS3 DNA methylation on T2DM: a case–control study

The mediation role of SOCS3 methylation in the effect of serum testosterone on type 2 diabetes

Androgen receptor DNA methylation is an independent determinant of glucose metabolic disorders in women; testosterone plays a moderating effect

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